Dosing & Uses
Dosage Forms & Strengths
tablet
- 12.5mg
- 25mg
- 50mg
- 100mg
Fibromyalgia
12.5 mg PO once on day 1, then 25 mg/day divided q12hr on days 2-3, then 50 mg/day divided q12hr on days 4-7, then 100 mg/day divided q12hr thereafter; not to exceed 200 mg/day
Therapy discontinuation
- When discontinuing antidepressant therapy that have lasted for more than 3 weeks, taper dose gradually over 2-4 weeks; this will minimize withdrawal symptoms and help detect reemerging symptoms
- If intolerable withdrawal symptoms occur, resume previously prescribed dose; may also decrease dose at more gradual rate; patients on long-term treatment (>6 weeks) may benefit from tapering over >3 months
Switching to or from MAO inhibitors
- Allow five or more days to elapse between milnacipran discontinuation and initiation of MAO inhibitor
- Allow 14 days to elapse between MAO inhibitor discontinuation and initiation of milnacipran
- Severe renal impairment: may increase to 50 mg BID if tolerated
Dosing Modifications
Renal impairment
- Mild (CrCl 50-80 mL/min): No dosage adjustment required
- Moderate (CrCl 30-49 mL/min): Use with caution
- Severe (CrCl 5-29 mL/min): Reduce maintenance dosage by 50% (ie, to 50 mg/day divided q12hr)
- End-stage renal disease (ESRD): Use not recommended
Hepatic impairment
- Mild or moderate (Child-Pugh A or B): No dosage adjustment required
- Severe (Child-Pugh C): Caution advised
<17 years: Safety and efficacy not established
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Contraindicated (7)
- iobenguane I 123
milnacipran decreases effects of iobenguane I 123 by pharmacodynamic antagonism. Contraindicated. If clinically appropriate, discontinue drugs that decrease uptake of NE for at least 5 half-lives; may cause false-negative imaging results.
- isocarboxazid
isocarboxazid and milnacipran both increase serotonin levels. Contraindicated.
- phenelzine
phenelzine and milnacipran both increase serotonin levels. Contraindicated.
- procarbazine
procarbazine and milnacipran both increase serotonin levels. Contraindicated. Combination is contraindicated within 2 weeks of MAOI use.
- rasagiline
rasagiline and milnacipran both increase serotonin levels. Contraindicated. Concomitant use with MAOIs or within 14 days of discontinuing treatment with an MAOI is contraindicated.
- safinamide
milnacipran, safinamide. Either increases toxicity of the other by serotonin levels. Contraindicated. Concomitant use could result in life-threatening serotonin syndrome.
- tranylcypromine
tranylcypromine and milnacipran both increase serotonin levels. Contraindicated.
Serious - Use Alternative (51)
- amitriptyline
milnacipran and amitriptyline both increase serotonin levels. Avoid or Use Alternate Drug.
- amoxapine
milnacipran and amoxapine both increase serotonin levels. Avoid or Use Alternate Drug.
- apixaban
milnacipran and apixaban both increase anticoagulation. Avoid or Use Alternate Drug.
- bupropion
milnacipran increases toxicity of bupropion by unspecified interaction mechanism. Avoid or Use Alternate Drug. May lower seizure threshold; keep bupropion dose as low as possible.
- buspirone
milnacipran and buspirone both increase serotonin levels. Avoid or Use Alternate Drug.
- citalopram
citalopram and milnacipran both increase serotonin levels. Avoid or Use Alternate Drug. Combination may increase risk of serotonin syndrome or neuroleptic malignant syndrome-like reactions.
- clomipramine
milnacipran and clomipramine both increase serotonin levels. Avoid or Use Alternate Drug.
- cyclobenzaprine
milnacipran and cyclobenzaprine both increase serotonin levels. Avoid or Use Alternate Drug.
- desipramine
milnacipran and desipramine both increase serotonin levels. Avoid or Use Alternate Drug.
- desvenlafaxine
milnacipran and desvenlafaxine both increase serotonin levels. Avoid or Use Alternate Drug.
- dextromethorphan
milnacipran and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.
- dolasetron
dolasetron, milnacipran. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug.
- dosulepin
milnacipran and dosulepin both increase serotonin levels. Avoid or Use Alternate Drug.
- doxepin
milnacipran and doxepin both increase serotonin levels. Avoid or Use Alternate Drug.
- duloxetine
duloxetine and milnacipran both increase serotonin levels. Avoid or Use Alternate Drug.
- epinephrine
milnacipran increases levels of epinephrine by pharmacodynamic synergism. Avoid or Use Alternate Drug. Risk of paroxysmal HTN, arrhythmia.
- epinephrine racemic
milnacipran increases levels of epinephrine racemic by pharmacodynamic synergism. Avoid or Use Alternate Drug. Risk of paroxysmal HTN, arrhythmia.
- escitalopram
escitalopram and milnacipran both increase serotonin levels. Avoid or Use Alternate Drug.
- fluoxetine
fluoxetine and milnacipran both increase serotonin levels. Avoid or Use Alternate Drug.
- fluvoxamine
fluvoxamine and milnacipran both increase serotonin levels. Avoid or Use Alternate Drug.
- granisetron
granisetron, milnacipran. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug.
- imipramine
milnacipran and imipramine both increase serotonin levels. Avoid or Use Alternate Drug.
- iobenguane I 131
milnacipran will decrease the level or effect of iobenguane I 131 by Other (see comment). Avoid or Use Alternate Drug. Based on the mechanism of action of iobenguane, drugs that reduce catecholamine uptake or that deplete catecholamine stores may interfere with iobenguane uptake into cells, and thus, reduce iobenguane efficacy. Discontinue interfering drugs for at least 5 half-lives before administration of either the dosimetry or an iobenguane dose. Do not administer these drugs until at least 7 days after each iobenguane dose.
- levomilnacipran
levomilnacipran and milnacipran both increase serotonin levels. Avoid or Use Alternate Drug.
- linezolid
linezolid and milnacipran both increase serotonin levels. Avoid or Use Alternate Drug. Linezolid may increase serotonin as a result of MAO-A inhibition. If linezolid must be administered, discontinue serotonergic drug immediately and monitor for CNS toxicity. Serotonergic therapy may be resumed 24 hours after last linezolid dose or after 2 weeks of monitoring, whichever comes first.
- lofepramine
milnacipran and lofepramine both increase serotonin levels. Avoid or Use Alternate Drug.
- lorcaserin
milnacipran and lorcaserin both increase serotonin levels. Avoid or Use Alternate Drug.
- maprotiline
milnacipran and maprotiline both increase serotonin levels. Avoid or Use Alternate Drug.
- meperidine
milnacipran and meperidine both increase serotonin levels. Avoid or Use Alternate Drug.
- methylene blue
methylene blue and milnacipran both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. If methylene blue must be administered, discontinue serotonergic drug immediately and monitor for CNS toxicity. Serotonergic therapy may be resumed 24 hours after last methylene blue dose or after 2 weeks of monitoring, whichever comes first.
- metoclopramide
metoclopramide and milnacipran both increase serotonin levels. Avoid or Use Alternate Drug. Additive effects; increased risk for serotonin syndrome, neuroleptic malignant syndrome, dystonia, or other extrapyramidal reactions
- nefazodone
milnacipran and nefazodone both increase serotonin levels. Avoid or Use Alternate Drug.
- netupitant/palonosetron
netupitant/palonosetron, milnacipran. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug.
- norepinephrine
milnacipran increases levels of norepinephrine by pharmacodynamic synergism. Avoid or Use Alternate Drug. Risk of paroxysmal HTN, arrhythmia.
- nortriptyline
milnacipran and nortriptyline both increase serotonin levels. Avoid or Use Alternate Drug.
- ondansetron
ondansetron, milnacipran. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug.
- ozanimod
ozanimod increases toxicity of milnacipran by sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Avoid or Use Alternate Drug. Because the active metabolite of ozanimod inhibits MAO-B in vitro, there is a potential for serious adverse reactions, including hypertensive crisis. Therefore, coadministration of ozanimod with drugs that can increase norepinephrine or serotonin is not recommended. Monitor for hypertension with concomitant use.
- palonosetron
palonosetron, milnacipran. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug.
- paroxetine
milnacipran and paroxetine both increase serotonin levels. Avoid or Use Alternate Drug.
- phentermine
milnacipran, phentermine. Either increases toxicity of the other by Mechanism: unknown. Avoid or Use Alternate Drug. Risk of serotonin syndrome.
- protriptyline
milnacipran and protriptyline both increase serotonin levels. Avoid or Use Alternate Drug.
- pseudoephedrine
milnacipran increases effects of pseudoephedrine by sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Avoid or Use Alternate Drug.
- selegiline
selegiline and milnacipran both increase serotonin levels. Avoid or Use Alternate Drug.
- selegiline transdermal
selegiline transdermal and milnacipran both increase serotonin levels. Avoid or Use Alternate Drug.
- sertraline
milnacipran and sertraline both increase serotonin levels. Avoid or Use Alternate Drug.
- St John's Wort
milnacipran and St John's Wort both increase serotonin levels. Avoid or Use Alternate Drug.
- trazodone
milnacipran and trazodone both increase serotonin levels. Avoid or Use Alternate Drug.
- trimipramine
milnacipran and trimipramine both increase serotonin levels. Avoid or Use Alternate Drug.
- venlafaxine
milnacipran and venlafaxine both increase serotonin levels. Avoid or Use Alternate Drug.
- vilazodone
milnacipran, vilazodone. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug. Concomitant therapy should be discontinued immediately if signs or symptoms of serotonin syndrome emerge and supportive symptomatic treatment should be initiated. .
- vortioxetine
milnacipran, vortioxetine. Either increases effects of the other by serotonin levels. Avoid or Use Alternate Drug.
Monitor Closely (109)
- 5-HTP
milnacipran and 5-HTP both increase serotonin levels. Modify Therapy/Monitor Closely.
- aceclofenac
milnacipran, aceclofenac. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.
- acemetacin
milnacipran, acemetacin. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.
- almotriptan
almotriptan and milnacipran both increase serotonin levels. Modify Therapy/Monitor Closely.
- aripiprazole
milnacipran, aripiprazole. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
- asenapine
milnacipran, asenapine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
- aspirin
milnacipran, aspirin. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.
- aspirin rectal
milnacipran, aspirin rectal. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.
- aspirin/citric acid/sodium bicarbonate
milnacipran, aspirin/citric acid/sodium bicarbonate. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.
- benzhydrocodone/acetaminophen
benzhydrocodone/acetaminophen, milnacipran. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration of drugs that affect the serotonergic neurotransmitter system may result in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment.
- buprenorphine subdermal implant
milnacipran, buprenorphine subdermal implant. Either increases toxicity of the other by serotonin levels. Use Caution/Monitor. Concomitant use could result in life-threatening serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation, and during dose adjustment of the serotonergic drug. Discontinue buprenorphine if serotonin syndrome is suspected.
- buprenorphine, long-acting injection
milnacipran, buprenorphine, long-acting injection. Either increases toxicity of the other by serotonin levels. Use Caution/Monitor. Concomitant use could result in life-threatening serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation, and during dose adjustment of the serotonergic drug. Discontinue buprenorphine if serotonin syndrome is suspected.
- cariprazine
milnacipran, cariprazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
- celecoxib
milnacipran, celecoxib. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.
- choline magnesium trisalicylate
milnacipran, choline magnesium trisalicylate. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.
- clomipramine
milnacipran, clomipramine. Mechanism: unspecified interaction mechanism. Use Caution/Monitor. Risk of euphoria, postural hypot'n when switching from clomipramine to milnacipran.
- clonidine
milnacipran decreases effects of clonidine by pharmacodynamic antagonism. Use Caution/Monitor.
- clopidogrel
milnacipran increases effects of clopidogrel by pharmacodynamic synergism. Use Caution/Monitor. SNRIs affect platelet activation; coadministration of SNRIs with clopidogrel may increase the risk of bleeding.
- clozapine
milnacipran, clozapine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
- cocaine topical
milnacipran and cocaine topical both increase serotonin levels. Modify Therapy/Monitor Closely.
- cyproheptadine
cyproheptadine decreases effects of milnacipran by pharmacodynamic antagonism. Use Caution/Monitor. Cyproheptadine may diminish the serotonergic effect of SNRIs.
- dexfenfluramine
milnacipran and dexfenfluramine both increase serotonin levels. Modify Therapy/Monitor Closely.
- dextroamphetamine
milnacipran and dextroamphetamine both increase serotonin levels. Modify Therapy/Monitor Closely.
- dextroamphetamine transdermal
milnacipran, dextroamphetamine transdermal. Either increases effects of the other by serotonin levels. Modify Therapy/Monitor Closely. Initiate with lower doses and monitor for signs and symptoms of serotonin syndrome, particularly during initiation or dosage increase. If serotonin syndrome occurs, discontinue dextroamphetamine transdermal and concomitant serotonergic drug(s).
- diazepam intranasal
diazepam intranasal, milnacipran. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration may potentiate the CNS-depressant effects of each drug.
- diclofenac
milnacipran, diclofenac. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.
- diflunisal
milnacipran, diflunisal. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.
- dihydroergotamine
milnacipran and dihydroergotamine both increase serotonin levels. Modify Therapy/Monitor Closely.
- dihydroergotamine intranasal
milnacipran and dihydroergotamine intranasal both increase serotonin levels. Modify Therapy/Monitor Closely.
- eletriptan
eletriptan and milnacipran both increase serotonin levels. Modify Therapy/Monitor Closely.
- ergotamine
milnacipran and ergotamine both increase serotonin levels. Modify Therapy/Monitor Closely.
- etodolac
milnacipran, etodolac. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.
- fenbufen
milnacipran, fenbufen. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.
- fenfluramine
milnacipran and fenfluramine both increase serotonin levels. Modify Therapy/Monitor Closely.
fenfluramine, milnacipran. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration with drugs that increase serotoninergic effects may increase the risk of serotonin syndrome. - fenoprofen
milnacipran, fenoprofen. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.
- fish oil triglycerides
fish oil triglycerides will increase the level or effect of milnacipran by anticoagulation. Use Caution/Monitor. Prolonged bleeding reported in patients taking antiplatelet agents or anticoagulants and oral omega-3 fatty acids. Periodically monitor bleeding time in patients receiving fish oil triglycerides and concomitant antiplatelet agents or anticoagulants.
- fluphenazine
milnacipran, fluphenazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
- flurbiprofen
milnacipran, flurbiprofen. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.
- frovatriptan
frovatriptan and milnacipran both increase serotonin levels. Modify Therapy/Monitor Closely.
- gabapentin
gabapentin, milnacipran. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of CNS depressants can result in serious, life-threatening, and fatal respiratory depression. Use lowest dose possible and monitor for respiratory depression and sedation.
- gabapentin enacarbil
gabapentin enacarbil, milnacipran. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of CNS depressants can result in serious, life-threatening, and fatal respiratory depression. Use lowest dose possible and monitor for respiratory depression and sedation.
- ganaxolone
milnacipran and ganaxolone both increase sedation. Use Caution/Monitor.
- green tea
green tea, milnacipran. Other (see comment). Use Caution/Monitor. Comment: Combination may increase risk of bleeding.
- haloperidol
milnacipran, haloperidol. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
- hydrocodone
hydrocodone, milnacipran. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration of drugs that affect the serotonergic neurotransmitter system may result in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment.
- ibrutinib
ibrutinib will increase the level or effect of milnacipran by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.
- ibuprofen
milnacipran, ibuprofen. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.
- ibuprofen IV
milnacipran, ibuprofen IV. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.
- iloperidone
milnacipran, iloperidone. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
- indomethacin
milnacipran, indomethacin. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.
- isoniazid
milnacipran and isoniazid both increase serotonin levels. Modify Therapy/Monitor Closely.
- ketoprofen
milnacipran, ketoprofen. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.
- ketorolac
milnacipran, ketorolac. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.
- ketorolac intranasal
milnacipran, ketorolac intranasal. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.
- L-tryptophan
milnacipran and L-tryptophan both increase serotonin levels. Modify Therapy/Monitor Closely.
- lasmiditan
lasmiditan, milnacipran. Either increases effects of the other by sedation. Use Caution/Monitor. Coadministration of lasmiditan and other CNS depressant drugs, including alcohol have not been evaluated in clinical studies. Lasmiditan may cause sedation, as well as other cognitive and/or neuropsychiatric adverse reactions.
milnacipran increases effects of lasmiditan by serotonin levels. Use Caution/Monitor. Coadministration may increase risk of serotonin syndrome. - lemborexant
lemborexant, milnacipran. Either increases effects of the other by sedation. Modify Therapy/Monitor Closely. Dosage adjustment may be necessary if lemborexant is coadministered with other CNS depressants because of potentially additive effects.
- lisdexamfetamine
milnacipran, lisdexamfetamine. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Initiate with lower doses and monitor for signs and symptoms of serotonin syndrome, particularly during initiation or dosage increase. If serotonin syndrome occurs, discontinue along with concomitant serotonergic drug(s).
- lithium
milnacipran and lithium both increase serotonin levels. Modify Therapy/Monitor Closely.
- lornoxicam
milnacipran, lornoxicam. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.
- loxapine
milnacipran, loxapine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
- loxapine inhaled
milnacipran, loxapine inhaled. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
- lsd
milnacipran and lsd both increase serotonin levels. Modify Therapy/Monitor Closely.
- lurasidone
lurasidone increases effects of milnacipran by Other (see comment). Use Caution/Monitor. Comment: Potential for additive CNS effects .
milnacipran, lurasidone. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction). - meclofenamate
milnacipran, meclofenamate. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.
- mefenamic acid
milnacipran, mefenamic acid. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.
- meloxicam
milnacipran, meloxicam. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.
- mirtazapine
milnacipran and mirtazapine both increase serotonin levels. Modify Therapy/Monitor Closely.
- molindone
milnacipran, molindone. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
- morphine
milnacipran and morphine both increase serotonin levels. Modify Therapy/Monitor Closely.
- nabumetone
milnacipran, nabumetone. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.
- naproxen
milnacipran, naproxen. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.
- naratriptan
naratriptan and milnacipran both increase serotonin levels. Modify Therapy/Monitor Closely.
- olanzapine
milnacipran, olanzapine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
- oliceridine
milnacipran, oliceridine. Either increases effects of the other by serotonin levels. Modify Therapy/Monitor Closely.
- oxaprozin
milnacipran, oxaprozin. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.
- paliperidone
milnacipran, paliperidone. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
- parecoxib
milnacipran, parecoxib. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.
- pentazocine
milnacipran and pentazocine both increase serotonin levels. Modify Therapy/Monitor Closely.
- perphenazine
milnacipran, perphenazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
- pimavanserin
milnacipran, pimavanserin. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
- pimozide
milnacipran, pimozide. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
- piroxicam
milnacipran, piroxicam. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.
- pregabalin
pregabalin, milnacipran. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of CNS depressants can result in serious, life-threatening, and fatal respiratory depression. Use lowest dose possible and monitor for respiratory depression and sedation.
- quetiapine
milnacipran, quetiapine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
- remifentanil
remifentanil increases toxicity of milnacipran by serotonin levels. Modify Therapy/Monitor Closely. Increases risk of serotonin syndrome.
- remimazolam
remimazolam, milnacipran. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely. Coadministration may result in profound sedation, respiratory depression, coma, and/or death. Continuously monitor vital signs during sedation and recovery period if coadministered. Carefully titrate remimazolam dose if administered with opioid analgesics and/or sedative/hypnotics.
- risperidone
milnacipran, risperidone. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
- rizatriptan
rizatriptan and milnacipran both increase serotonin levels. Modify Therapy/Monitor Closely.
- salicylates (non-asa)
milnacipran, salicylates (non-asa). Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.
- salsalate
milnacipran, salsalate. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.
- SAMe
milnacipran and SAMe both increase serotonin levels. Modify Therapy/Monitor Closely.
- sodium sulfate/potassium chloride/magnesium sulfate/polyethylene glycol
milnacipran, sodium sulfate/potassium chloride/magnesium sulfate/polyethylene glycol. Other (see comment). Use Caution/Monitor. Comment: Caution when bowel preps are used with drugs that cause SIADH or NSAIDs; increased risk for water retention or electrolyte imbalance.
- sufentanil SL
sufentanil SL, milnacipran. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration of drugs that affect the serotonergic neurotransmitter system may result in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment.
- sulfasalazine
milnacipran, sulfasalazine. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.
- sulindac
milnacipran, sulindac. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.
- sumatriptan
sumatriptan and milnacipran both increase serotonin levels. Modify Therapy/Monitor Closely.
- sumatriptan intranasal
sumatriptan intranasal and milnacipran both increase serotonin levels. Modify Therapy/Monitor Closely.
- tapentadol
milnacipran and tapentadol both increase serotonin levels. Modify Therapy/Monitor Closely.
- thiothixene
milnacipran, thiothixene. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
- tolfenamic acid
milnacipran, tolfenamic acid. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.
- tolmetin
milnacipran, tolmetin. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.
- tramadol
milnacipran and tramadol both increase serotonin levels. Modify Therapy/Monitor Closely.
- trifluoperazine
milnacipran, trifluoperazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
- valerian
valerian and milnacipran both increase sedation. Use Caution/Monitor.
- vorapaxar
milnacipran, vorapaxar. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Additive antiplatelet effect may occur; SSRIs and SNRIs may cause platelet serotonin depletion .
- warfarin
milnacipran, warfarin. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Serotonin release by platelets plays an important role in hemostasis. SSRIs and SNRIs may increase anticoagulation effect of warfarin. .
- ziprasidone
milnacipran, ziprasidone. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
- zolmitriptan
zolmitriptan and milnacipran both increase serotonin levels. Modify Therapy/Monitor Closely.
Minor (18)
- almotriptan
milnacipran, almotriptan. Mechanism: unknown. Minor/Significance Unknown. Risk of weakness, dyspnea, chest pain.
- bumetanide
bumetanide, milnacipran. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Possible additive hyponatremia.
- celandine
celandine decreases effects of milnacipran by pharmacodynamic antagonism. Minor/Significance Unknown. Based on animal studies.
- dexmethylphenidate
dexmethylphenidate increases effects of milnacipran by decreasing metabolism. Minor/Significance Unknown.
- eletriptan
milnacipran, eletriptan. Mechanism: unknown. Minor/Significance Unknown. Risk of weakness, dyspnea, chest pain.
- ethacrynic acid
ethacrynic acid, milnacipran. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Possible additive hyponatremia.
- frovatriptan
milnacipran, frovatriptan. Mechanism: unknown. Minor/Significance Unknown. Risk of weakness, dyspnea, chest pain.
- furosemide
furosemide, milnacipran. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Possible additive hyponatremia.
- lithium
milnacipran, lithium. Mechanism: unknown. Minor/Significance Unknown. Risk of neurotoxicity.
- naratriptan
milnacipran, naratriptan. Mechanism: unknown. Minor/Significance Unknown. Risk of weakness, dyspnea, chest pain.
- panax ginseng
panax ginseng increases effects of milnacipran by pharmacodynamic synergism. Minor/Significance Unknown.
- pleurisy root
pleurisy root decreases effects of milnacipran by unspecified interaction mechanism. Minor/Significance Unknown. Theoretical interaction.
- rizatriptan
milnacipran, rizatriptan. Mechanism: unknown. Minor/Significance Unknown. Risk of weakness, dyspnea, chest pain.
- serdexmethylphenidate/dexmethylphenidate
serdexmethylphenidate/dexmethylphenidate increases effects of milnacipran by decreasing metabolism. Minor/Significance Unknown.
- sumatriptan
milnacipran, sumatriptan. Mechanism: unknown. Minor/Significance Unknown. Risk of weakness, dyspnea, chest pain.
- sumatriptan intranasal
milnacipran, sumatriptan intranasal. Mechanism: unknown. Minor/Significance Unknown. Risk of weakness, dyspnea, chest pain.
- torsemide
torsemide, milnacipran. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Possible additive hyponatremia.
- zolmitriptan
milnacipran, zolmitriptan. Mechanism: unknown. Minor/Significance Unknown. Risk of weakness, dyspnea, chest pain.
Adverse Effects
>10%
Nausea (37%)
Headache (18%)
Constipation (16%)
Hot flush (12%)
Insomnia (12%)
1-10% (selected)
Dizziness
Hyperhidrosis
Hypertension
Migraine
Palpitations
Tachycardia
Vomiting
Xerostomia
Frequency Not Defined
Abnormal bleeding
Depression (worsening)
Serotonin syndrome
Suicidal thoughts
Withdrawal signs or symptoms
Postmarketing Reports
Hematologic disorders: Leukopenia, neutropenia, thrombocytopenia
Cardiac disorders: Supraventricular tachycardia, takotsubo cardiomyopathy
Eye disorders: Accommodation disorder
Endocrine disorders: Hyperprolactinemia
Gastrointestinal disorders: Acute pancreatitis
Hepatobiliary disorders: Hepatitis
Metabolic and nutritional disorders: Anorexia, hyponatremia
Musculoskeletal and connective tissue disorders: Rhabdomyolysis
Neurologic disorders: Convulsions (including grand mal), loss of consciousness, parkinsonism, hyposmia, anosmia
Psychiatric disorders: Aggression, anger, delirium, hallucination, homicidal ideation
Renal and urinary disorders: Acute renal failure
Reproductive system and breast disorders: Galactorrhea, decreased libido, delayed or absent orgasm
Skin disorders: Erythema multiforme, Stevens-Johnson syndrome
Vascular disorders: Hypertensive crisis
Warnings
Black Box Warnings
In short-term studies, antidepressants increased risk of suicidal thinking and behavior in children, adolescents, and young (<24 years) adults taking antidepressants for major depressive disorders and other psychiatric illnesses
This increase was not seen in patients aged >24 years; slight decrease in suicidal thinking was seen in adults aged >65 years
In children and young adults, risks must be weighed against benefits of taking antidepressants
Patients should be monitored closely for changes in behavior, clinical worsening, and suicidal tendencies; this should be done during initial 1-2 months of therapy and dosage adjustments
Patient’s family should communicate any abrupt behavioral changes to healthcare provider
Worsening behavior and suicidal tendencies that are not part of presenting symptoms may necessitate discontinuance of therapy
Drug is not approved for use in pediatric patients
Contraindications
Concomitant use of monoamine oxidase inhibitors (MAOIs), use of MAOIs within 5 days after discontinuance of milnacipran, or initiation of milnacipran within 14 days after discontinuance of MAOIs
Patients being treated with linezolid or intravenous methylene blue
Cautions
Milnacipran is serotonin-norepinephrine reuptake inhibitor (SNRI) similar to those used for depression and other psychiatric disorders; monitoring and close observation for clinical worsening, suicidality, and unusual changes in behavior are necessary, especially during first few months of treatment and when dosage is increased or decreased (see Black Box Warnings)
Potentially life-threatening serotonin syndrome has been reported with both SNRIs and selective serotonin reuptake inhibitors (SSRIs) when these agents are taken alone, but especially when they are coadministered with other serotonergic agents; thus, patient medications should be thoroughly reviewed for other serotonergic drugs (eg, tryptophan supplements, tramadol, serotonin agonists [triptans], MAOIs, tricyclic antidepressants [TCAs], SSRIs, methylene blue, meperidine, methadone, buspirone, amphetamines, linezolid); serotonin syndrome can also occur when these drugs are used alone
May increase blood pressure (BP) or heart rate (HR); BP should be controlled before initiation of milnacipran; BP and HR should be monitored while patient is taking drug; consider dose reduction or discontinuation of therapy in patients with sustained hypertension or tachycardia during therapy
SSRIs and SNRIs may impair platelet aggregation and increase the risk of bleeding events, ranging from ecchymoses, hematomas, epistaxis, petechiae, and GI hemorrhage to life-threatening hemorrhage; concomitant use of aspirin, NSAIDs, warfarin, other anticoagulants, or other drugs known to affect platelet function may add to this risk; inform patients about increased risk of bleeding associated with concomitant use with NSAIDs, aspirin, or other drugs that affect coagulation
Neonates exposed to SNRIs or SSRIs late in third trimester are at risk for complications such as feeding difficulties, irritability, and respiratory problems
Prescription should be written for smallest amount consistent with good patient care; alert family members to monitor for emergence of suicidality, including panic attacks, hostility, irritability, insomnia, anxiety, agitation, mania and hypomania
Bone fracture reported with antidepressant treatment; consider possibility of fracture in patients that present with unexplained bone pain, swelling, or bruising
Use caution in patients with history of seizures
Moderate renal impairment
Avoid use in severe hepatic impairment; discontinue therapy with signs of hepatic dysfunction or jaundice; do not reinitiate therapy unless another source or cause identified
Avoid concomitant use in patients with substantial alcohol use or chronic liver disease
Withdrawal symptoms reported in patients when discontinuing treatment; gradual dose reduction recommended
Pupillary dilation that occurs following use of SNRI drugs including milnacipran may trigger angle closure attack in patients with anatomically narrow angles who do not have a patent iridectomy; for patients who have not had an iridectomy for narrow-angle glaucoma risk factors, consider performing evaluation
Patietns with history of obstructive uropathies may experience higher rates of genitourinary adverse drug reactions (ADRs)
ESRD: Use not recommended
Development of SIADH and hyponatremia reported with SSRIs and SNRIs, predominantly in the elderly; volume depletion and/or concurrent use of diuretics may increase risk
May cause urinary hesitance; advise patients to report urinary symptoms or difficulties; use caution in patients with history of lower urinary tract disorders, including benign prostatic hyperplasia or prostatitis
May worsen psychosis in patients with mood disorders; a shift to mania or hypomania reported with bipolar disorder; avoid monotherapy in patients with bipolar disorder; screen prospective patients for bipolar disorder when presenting with depressive symptoms
Sexual dysfunction
- In female patients, SSRI/SNRI use may result in decreased libido and delayed or absent orgasm
- Important for prescribers to inquire about sexual function prior to initiation of therapy and to inquire specifically about changes in sexual function during treatment, because sexual function may not be spontaneously reported
- When evaluating changes in sexual function, obtaining a detailed history (including timing of symptom onset) is important because sexual symptoms may have other causes, including underlying psychiatric disorder
- Discuss potential management strategies to support patients in making informed decisions about treatment
Pregnancy & Lactation
Pregnancy
There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to this drug during pregnancy
Physicians are advised to recommend that pregnant patients taking SAVELLA enroll in the Savella Pregnancy Registry; enrollment is voluntary and may be initiated by pregnant patients or their healthcare providers by contacting the registry at 1-877-643-3010 or by email at pregnancyregistries@incresearch.com; data forms may also be downloaded from the registry website at www.savellapregnancyregistry.com
Based on data from published observational studies, exposure to SSRIs, particularly in the month before delivery, has been associated with < 2-fold increase in risk of postpartum hemorrhage
The available data on use in pregnant women are insufficient to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes; there are risks associated with exposure to serotonin and norepinephrine reuptake inhibitors (SNRIs) and selective serotonin reuptake inhibitors (SSRIs); including this drug, during pregnancy
Animal data
- Animal reproduction studies have been performed in rats, rabbits and mice; this drug was shown to increase embryofetal and perinatal lethality in rats and the incidence of a minor skeletal variation in rabbits at doses below (rat) or approximately equal to(rabbit) the maximum recommended human dose (MRHD) of 200 mg/day on a mg/m2 basis; no effects were seen in mice when treated with milnacipran during the period of organogenesis at doses up to 3 times MHRD on a mg/m2 basis
- Therapy in the month before delivery may be associated with an increased risk of postpartum hemorrhage
- Neonates exposed to SNRIs or SSRIs, including this drug, late in the third trimester have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding
- Such complications can arise immediately upon delivery; reported clinical findings have included respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypotonia, hypertonia, hyperreflexia, tremor, jitteriness, irritability, and constant crying
- These findings are consistent with either direct toxic effect of SSRIs and SNRIs or possibly, a drug discontinuation syndrome; it should be noted that, in some cases, the clinical picture is consistent with serotonin syndrome
Lactation
This drug is present in human milk; there are no reports on effects of therapy on the breastfed child and on milk production/excretion
However, there are reports of agitation, irritability, poor feeding, and poor weight gain in infants exposed to SSRIs or SNRIsthrough breast milk
The developmental and health benefits of breastfeeding should be considered along with mother’s clinical need for therapy and any potential adverse effects on breastfed child from this drug or from underlying maternal conditions
Monitor infants exposed to this drug for agitation, irritability, poor feeding and poor weight gain
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
Mechanism of Action
SNRI; has no affinity for other neurotransmitter receptors (including gamma-aminobutyric acid [GABA], beta-adrenergic, opiate, histaminergic, and benzodiazepine receptors) and has no MAOI activity
Absorption
Bioavailability: 85-90%
Peak plasma time: 2-4 hr
Distribution
Protein bound: 13%
Vd: 400 L
Metabolism
Metabolized to several metabolites
Elimination
Half-life: L-isomer, 6-8 hr; D-isomer, 8-10 hr
Excretion: Urine (55%)
Images
| BRAND | FORM. | UNIT PRICE | PILL IMAGE |
|---|---|---|---|
| Savella oral - | 12.5 mg tablet |  | |
| Savella oral - | 100 mg tablet |  | |
| Savella oral - | 12.5 mg (5)-25 mg(8)-50 mg(42) tablet |  | |
| Savella oral - | 25 mg tablet |  | |
| Savella oral - | 50 mg tablet |  |
Copyright © 2010 First DataBank, Inc.
Patient Handout
milnacipran oral
MILNACIPRAN - ORAL
(mil-NA-si-pran)
COMMON BRAND NAME(S): Savella
WARNING: Although not used for depression, this medication is in the same class as antidepressant medications. Antidepressant medications are used to treat a variety of conditions, including depression and other mental/mood disorders. These medications can help prevent suicidal thoughts/attempts and provide other important benefits. However, studies have shown that a small number of people (especially people younger than 25) who take antidepressants for any condition may experience worsening depression, other mental/mood symptoms, or suicidal thoughts/attempts. It is very important to talk with the doctor about the risks and benefits of antidepressant medication (especially for people younger than 25), even if treatment is not for a mental/mood condition.Tell the doctor right away if you notice worsening depression/other psychiatric conditions, unusual behavior changes (including possible suicidal thoughts/attempts), or other mental/mood changes (including new/worsening anxiety, panic attacks, trouble sleeping, irritability, hostile/angry feelings, impulsive actions, severe restlessness, very rapid speech). Be especially watchful for these symptoms when a new antidepressant is started or when the dose is changed.
USES: Milnacipran is used to treat pain caused by a condition called fibromyalgia that affects the muscles, tendons, ligaments, and supporting tissues.This medication is a serotonin-norepinephrine reuptake inhibitor (SNRI) that works by helping to restore the balance of certain natural substances in the brain (neurotransmitters).
HOW TO USE: Read the Medication Guide provided by your pharmacist before you start using milnacipran and each time you get a refill. If you have any questions, consult your doctor or pharmacist.Take this medication by mouth with or without food as directed by your doctor, usually 2 times a day. If you have nausea, it may help to take this medication with food.Dosage is based on your medical condition and response to treatment.To reduce your risk of side effects, your doctor may start you at a low dose and gradually increase your dose. Follow your doctor's instructions carefully. Do not increase your dose or take this medication more often than prescribed. Your condition will not improve any faster, and the risk of serious side effects may be increased.If you suddenly stop using this medication, you may have withdrawal symptoms (such as mood swings, headache, tiredness, sleep changes, brief feelings similar to electric shock). To help prevent withdrawal, your doctor may lower your dose slowly. Withdrawal is more likely if you have used milnacipran for a long time or in high doses. Tell your doctor or pharmacist right away if you have withdrawal.Tell your doctor if your condition does not improve or if it worsens.
SIDE EFFECTS: See also Warning section.Nausea, vomiting, dry mouth, constipation, loss of appetite, dizziness, increased sweating, headache, or hot flashes (flushing) may occur. If any of these effects last or get worse, tell your doctor promptly.Remember that this medication has been prescribed because your doctor has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.This medication may raise your blood pressure. Check your blood pressure regularly and tell your doctor if the results are high.Tell your doctor right away if you have any serious side effects, including: fast/pounding heartbeat, changes in sexual ability, decreased interest in sex, painful/difficult urination, seizures, yellowing eyes/skin, dark urine, severe stomach/abdominal pain, easy bleeding/bruising.Get medical help right away if you have any very serious side effects, including: black stools, vomit that looks like coffee grounds, eye pain/swelling/redness, widened pupils, vision changes (such as seeing rainbows around lights at night, blurred vision).This medication may increase serotonin and rarely cause a very serious condition called serotonin syndrome/toxicity. The risk increases if you are also taking other drugs that increase serotonin, so tell your doctor or pharmacist of all the drugs you take (see Drug Interactions section). Get medical help right away if you develop some of the following symptoms: fast heartbeat, hallucinations, loss of coordination, severe dizziness, severe nausea/vomiting/diarrhea, twitching muscles, unexplained fever, unusual agitation/restlessness.A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.In the US -Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch.In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.
PRECAUTIONS: Before taking milnacipran, tell your doctor or pharmacist if you are allergic to it; or to levomilnacipran; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.Before using this medication, tell your doctor or pharmacist your medical history, especially of: kidney disease, liver disease, alcohol use, personal or family history of glaucoma (angle-closure type), personal or family history of psychiatric disorders (such as bipolar/manic-depressive disorder), personal or family history of suicide attempts, high blood pressure, heart problems (such as chest pain, heart attack, fast/irregular heartbeat), seizure disorder, dehydration, intestinal ulcers/bleeding (peptic ulcer disease), mineral imbalance (low level of sodium in the blood), painful/difficult urination (for example, due to enlarged prostate).This drug may make you dizzy. Alcohol or marijuana (cannabis) can make you more dizzy. Do not drive, use machinery, or do anything that needs alertness until you can do it safely. Avoid alcoholic beverages. Talk to your doctor if you are using marijuana (cannabis). Drinking alcohol can also increase your risk of liver problems.Before having surgery, tell your doctor or dentist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products).Older adults may be more sensitive to the side effects of this drug, especially bleeding. Older adults may also be at greater risk for mineral imbalance (low level of sodium in the blood) while using this drug, especially if they are also taking "water pills" (diuretics) with this medication.During pregnancy, this medication should be used only when clearly needed. Discuss the risks and benefits with your doctor. Babies born to mothers who have used this drug during the last 3 months of pregnancy may rarely develop withdrawal symptoms such as feeding/breathing difficulties, seizures, muscle stiffness, or constant crying. If you notice any of these symptoms in your newborn, tell the doctor promptly.This medication passes into breast milk. Consult your doctor before breast-feeding.
DRUG INTERACTIONS: Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor's approval.Some products that may interact with this drug are: "water pills" (diuretics such as furosemide), other drugs that can cause bleeding/bruising (including antiplatelet drugs such as clopidogrel, NSAIDs such as ibuprofen/naproxen, "blood thinners" such as dabigatran/warfarin).Taking MAO inhibitors with this medication may cause a serious (possibly fatal) drug interaction. Avoid taking MAO inhibitors (isocarboxazid, linezolid, metaxalone, methylene blue, moclobemide, phenelzine, procarbazine, rasagiline, safinamide, selegiline, tranylcypromine) during treatment with this medication. Most MAO inhibitors should also not be taken for two weeks before and at least 5 days after treatment with this medication. Ask your doctor when to start or stop taking this medication.Aspirin can increase the risk of bleeding when used with this medication. However, if your doctor has directed you to take low-dose aspirin for heart attack or stroke prevention (usually 81-162 milligrams a day), you should continue taking it unless your doctor instructs you otherwise. Ask your doctor or pharmacist for more details.The risk of serotonin syndrome/toxicity increases if you are also taking other drugs that increase serotonin. Examples include street drugs such as MDMA/"ecstasy," St. John's wort, certain antidepressants (including SSRIs such as fluoxetine/paroxetine, other SNRIs such as duloxetine/venlafaxine), tryptophan, among others. The risk of serotonin syndrome/toxicity may be more likely when you start or increase the dose of these drugs.Milnacipran is very similar to levomilnacipran. Do not use medications containing levomilnacipran while using milnacipran.
OVERDOSE: If someone has overdosed and has serious symptoms such as passing out or trouble breathing, call 911. Otherwise, call a poison control center right away. US residents can call their local poison control center at 1-800-222-1222. Canada residents can call a provincial poison control center. Symptoms of overdose may include: confusion, severe drowsiness/dizziness.
NOTES: Do not share this medication with others.Lab and/or medical tests (such as blood pressure, heart rate, liver function) should be done while you are taking this medication. Keep all medical and lab appointments. Consult your doctor for more details.
MISSED DOSE: If you miss a dose, take it as soon as you remember. If it is near the time of the next dose, skip the missed dose. Take your next dose at the regular time. Do not double the dose to catch up.
STORAGE: Store at room temperature away from light and moisture. Do not store in the bathroom. Keep all medications away from children and pets.Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company.
Information last revised May 2023. Copyright(c) 2023 First Databank, Inc.
IMPORTANT: HOW TO USE THIS INFORMATION: This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.
Formulary
Adding plans allows you to compare formulary status to other drugs in the same class.
To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.
Adding plans allows you to:
- View the formulary and any restrictions for each plan.
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